Individual differences in male rat ejaculatory behaviour: searching for models to study ejaculation disorders

In addition to investigating sexual function in rats that display normal ejaculatory behaviour, studying rats that are either 'hyposexual' or 'hypersexual' may provide important insights into the aetiology of ejaculatory dysfunctions in men, such as premature and retarded ejaculation. To this end, rats were matched into groups of 'sluggish', 'normal' and 'rapid' ejaculators based on their ejaculation frequencies displayed in a series of weekly sexual behaviour tests. Selecting rats on this parameter revealed large and stable differences in other parameters of sexual behaviour as well, including ejaculation latency and mount frequency but not intromission frequency and mount latency, putative indices of sexual motivation. Neuroanatomically, Fos immunoreactivity as a measure of neuronal activation was increased in rapid ejaculators compared with sluggish ejaculators in ejaculation-related brain areas, presumably associated with the differences in ejaculatory behaviour. Although the total number of oxytocin neurones within subregions of the hypothalamus did not differ between groups, in the supraoptic nucleus of the hypothalamus more oxytocin neurones were activated in rapid ejaculators compared with the other groups. Apart from the differences observed in ejaculatory behaviour, groups did not differ with respect to their locomotor activity and approach-avoidance behaviour as measured in the elevated plus-maze. Finally, apomorphine-induced stereotypy was similar in sluggish and rapid ejaculators, suggesting no large differences in dopamine susceptibility. Altogether, the present results suggest stable differences in male rat ejaculatory behaviour. Further exploring the neurobiological mechanisms underlying these differences may be a promising approach to gain insights into the aetiology of sexual dysfunctions such as premature, retarded or an-ejaculation.     

Lesions of the nucleus paragigantocellularis: effects on mating behavior in male rats

We evaluated the effects of bilateral radio-frequency lesions of the paragigantocellular (PGi) reticular nucleus in the ventral medulla on male rat copulatory behavior. In Experiment 1, sexually naive male rats with such lesions were more likely than sham-operated controls to copulate to ejaculation during their first exposure to an estrous female. Additionally, among the rats that copulated to ejaculation, those with lesions demonstrated a reduction in mount frequency (MF), intromission frequency (IF), and ejaculation latency (EL), and an increase in copulatory efficiency (CE). In Expt. 2, sexually experienced male rats were allowed to mate to sexual exhaustion. Males with PGi lesions showed an increased latency to sexual exhaustion and an increased number of ejaculations prior to exhaustion. Additionally, rats with PGi lesions displayed reductions in IF, EL, and post-ejaculatory interval (PEI) as they approached sexual exhaustion. Our results provide further evidence that the PGi is a supraspinal locus of descending inhibitory influence on spinal nuclei mediating ejaculatory reflexes in the male rat.     

The effects of idazoxan and 8-OH-DPAT on sexual behaviour and associated ultrasonic vocalizations in the rat

Two experiments were performed studying the effects of 8-OH-DPAT and idazoxan on sexual behaviour and ultrasonic communication of male rats. In addition, the reactions of the females towards drug-treated males were studied. 8-OH-DPAT (a very specific 5-HT1A agonist) and idazoxan (an alpha 2-adrenergic antagonist) differentially affected sexual behaviour: 8-OH-DPAT (0.1 and 0.4 mg/kg IP) markedly facilitated ejaculations, a feature indicated by decreased numbers of mounts and intromissions preceding ejaculation and a reduction in ejaculation latency. This drug concomitantly reduced the postejaculatory refractory period. Idazoxan reduced the number of intromissions before ejaculation only at the highest dose (10 mg/kg IP), but did not markedly facilitate other parameters. Both drugs markedly and dose-dependently suppressed the postejaculatory 22 kHz ultrasounds normally recorded during the postejaculatory refractory period. Ultrasound frequencies above 30 kHz first appear at the end of the absolute refractory period, even when the refractory period is shortened by 8-OH-DPAT. Idazoxan increased the number of these 30 kHz ultrasounds, whereas 8-OH-DPAT had no effect on them. No effects were observed on ultrasound production (either 22 kHz or above 30 kHz) before an ejaculation. The behaviour of the females towards 8-OH-DPAT-treated males was also affected, with the females showing more darting and lordosis before and after ejaculation, but less sitting after ejaculation. Idazoxan treatment of the males resulted in more hopping and earwiggling of the females before ejaculation. Following ejaculation, females treated with the antagonist showed more darting, hopping, earwiggling and lordosis, but sitting was decreased. It has been suggested in the rat that the emergence of ultrasounds higher than 30 kHz indicates the end of the absolute refractory period and signals to the female that the male is capable of resuming sexual activity. The significance of 22 kHz ultrasound in sexual behaviour remains puzzling because these vocalizations could be easily uncoupled from the refractory period by drugs acting via different receptor mechanisms without disturbing sexual behaviour per se. A failure to produce postejaculatory sounds appears to disinhibit (proceptive) behaviour by the females.     

Antagonism by pindolol,but not betaxolol,of 8-OH-DPAT-induced facilitation of male rat sexual behavior

Summary 8-OH-DPAT (0.25 mg/kg s.c.) produced a facilitation of the male rat sexual behavior, characterized by a decrease in the number of intromissions preceding ejaculation and in the time to ejaculation. This facilitation of the sexual behavior was antagonized by administration of the 5-HT and -adrenoceptor antagonist pindolol (4mg/kg i.p.), but not by the selective -adrenoceptor antagonist betaxolol (4 mg/kg i.p.). Neither pindolol (2–8 mg/kg), nor betaxolol (2–8 mg/kg), produced any statistically significant effects per se on the male rat sexual behavior, as observed here (mounts, intromissions, ejaculation latency or the post-ejaculatory interval). A higher dose (16mg/kg) of betaxolol produced a statistically significant reduction in the number of intromissions preceding ejaculation and in the ejaculation latency. The antagonism by pindolol of 8-OH-DPAT-induced effects on male rat sexual behavior suggests an involvement of 5-HT_1A receptors in the facilitation of this behavior produced by 8-OH-DPAT.     

Central neurophysiology and dopaminergic control of ejaculation

Although premature ejaculation (PE) represents the most common male sexual dysfunction, brain mechanisms controlling ejaculatory process remain poorly understood. Recently a group of neurons, identified in the lumbar spinal cord, has been proposed to constitute a spinal ejaculation generator. This key site in ejaculation control, relaying sensory inputs to the brain, is under supraspinal excitatory (medial preoptic area, paraventricular nucleus of the hypothalamus) and inhibitory (nucleus paragigantocellularis) controls. Activation of brain excitatory areas by dopamine (DA) or DA agonists being demonstrated to facilitate ejaculation, it seems particularly interesting to further understand the implication of central DA in the complex process leading to ejaculation. Moreover, the fact that dopaminergic pathways are involved in sexual behavior and that DA release in some brain regions is an important facilitator of male sexual behavior reinforces the crucial implication of DA. Clearly, a better understanding of DA incerto-hypothalamic pathways and targeting brain DA receptor subtypes mediating ejaculation (especially D(3) receptors) will benefit the development of new pharmacological strategies to treat ejaculatory dysfunction including PE.     

Sexual motivation: a neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats

Experiments investigating the neural mechanisms underlying the expression of masculine sexual behaviour are discussed in the context of the hypothesis set out by Frank Beach that suggested the existence of separate sexual arousal and performance mechanisms. The results indicate that the medial preoptic area is crucially involved in consummatory aspects of sexual behaviour: lesions and chemical manipulations of the area profoundly affect mounts, intromissions and ejaculation, but tend not to alter appetitive sexual responses. By contrast, ventral striatal dopamine-dependent mechanisms primarily affect appetitive sexual responses, measured in a variety of paradigms, but tend not to alter copulatory behaviour itself. Finally, associative mechanisms, for example those by which arbitrary environmental stimuli come to control appetitive sexual responses through their predictive association with sexual reinforcement, are shown to depend at least in part on interactions between the basolateral amygdala and dopamine-dependent events in the ventral striatum. Thus, diverse neural and behavioural procedures have revealed that separable neural mechanisms appear to be involved more or less selectively with different components of the male rat's sexual response system. It may still be useful to conceptualize separate sexual arousal and intromission/ejaculatory mechanisms when studying the neuroendocrine basis of sexual behaviour. However, a major challenge is to understand the way in which elements of the telencephalic limbic system, the striatum and preoptic area, some of which are targets for the action of sex steroids, interact to produce an integrated pattern of sexual behaviour.     

Noradrenaline-serotonin interactions in the control of sexual behavior in the male rat: DSP4-induced noradrenaline depletion antagonizes the facilitatory effect of serotonin receptor agonists, 5-MeODMT and lisuride

The present communication reports how depletion of central noradrenaline neurons of DSP4 treatment antagonizes the facilitatory actions of 5-MeODMT and lisuride on male rat sexual behavior. In males with intact noradrenaline, 5-MeODMT facilitated sexual behavior by reducing the number of intromissions required for ejaculation; inhibitory actions were also noted, since 5-MeODMT prolonged intromission and ejaculation latencies. In DSP4-pretreated animals the inhibitory effect of 5-MeODMT remained unchanged, whereas its facilitatory action was abolished. Consistent with previous research, lisuride also reduced intromission frequency prior to ejaculation. This facilitation of sexual behavior was not observed in DSP4-treated animals. In the male rat, ejaculations following the first have a lower latency and are preceded by a lower number of intromissions. This naturally occurring facilitation of sexual behavior was not prevented by DSP4-induced noradrenaline depletion. Our results suggest that serotonin and noradrenaline interact in the control of sexual behavior in the male rat.     

Evidence for the presence of the spinal pattern generator involved in the control of the genital ejaculatory pattern in the female rat

Substantial progress has been made during recent years in elucidating the control of male ejaculatory function by the central nervous system. These efforts have revealed the participation of a central pattern generator in the control of ejaculation. There is a strong similarity in the neural organization of male and female sexual functions. In the present study, the hypothesis that the spinal generator for ejaculation was present and functional in the female rat was evaluated. To this purpose, the expression of the ejaculatory motor pattern and its pharmacological activation in spinally transected female rats were investigated. Results revealed the presence in females of the already described rhythmic ejaculatory motor pattern of male rats. This ejaculatory motor pattern could be registered in the urethralis muscle of the female rat after mechanical stimulation of the urethra, vagina and clitoris and consisted, as in the male rat, of a first ejaculatory motor train followed by an after-discharge component. Besides, the female genital ejaculatory motor pattern could be pharmacologically induced by the systemic injection of sodium nitroprusside with similar motor characteristics. No significant differences between the sensorial and pharmacologically induced female genital motor patterns were found. Present findings provide evidence for the presence of the genital motor pattern of ejaculation in female rats and suggest that the spinal generator for ejaculation is also present and functional in this gender.     

Dose-dependent effects of acute kainic acid treatment on sexual behavior of male rats

Male rats of the Wistar strain were selected as good copulators (displaying at least 1 ejaculation in each of three consecutive tests for male sexual behavior) and sexually sluggish animals (displaying no ejaculations in each of three consecutive tests). The administration of low doses (1 and 2.5 mg/kg, i.p.) of kainic acid in sexually sluggish rats induced an enhancement of some parameters of copulatory behavior. In particular, significant reductions in latency to the first mount and intromission and increases in frequency of mounts and intromissions were observed. In contrast, the drug failed to exert any effect in good copulators. At the dose of 5 mg/kg (i.p.) kainic acid exerted an inhibitory effect on sexual behavior parameters both in good copulators and in sluggish rats. A persistent increase in latency to the first mount, intromission and ejaculation, and reduction in frequency of mounts, intromissions and ejaculation both in good copulators and in sluggish rats were observed 20 days after kainic acid treatment at the higher dose. No persistent effect of kainic acid 1 and 2.5 mg/kg was observed 20 days after treatment. These results suggest that kainic acid may affect in a dose-dependent manner several copulatory parameters of male sexual behavior repertoire. The bimodal effects could be explained considering a possible interaction of kainic acid with different neurotransmissions or receptor subtypes.     

Effects of pergolide and bromocriptine on male rat sexual behavior

Summary Intact adult male rats were treated with bromocriptine 0–20 mg/kg and pergolide 0–3.2 mg/kg. Two hours after the injection of the respective drug the male rat was presented with a receptive female and various components of the sexual behavior were recorded. Pergolide produced a dose-dependent decrease in the number of intromissions preceding ejaculation and a shortening of the ejaculation latency. The only effect observed after the injection of bromocriptine was an increase in the post-ejaculatory interval at high doses.     

Morphine and dynorphin(1–13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01–6 nmol) and dynorphin(1–13) (0.01–3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10–100 pmol) and dynorphin (10–100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1–10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.     

Region-selective inhibition of male rat sexual behavior and motor performance by localized forebrain 5-HT injections: a comparison with effects produced by 8-OH-DPAT.

The local application of 5-HT (0-40 micrograms side-1) into the nucleus accumbens was found to inhibit male rat sexual behavior, as evidenced by an increase in number of mounts and intromissions preceding ejaculation and in time to ejaculation. There were no effects on male rat sexual behavior after similar 5-HT injections into other striatal areas, including the dorsolateral, the ventromedial and the posterior neostriatum, as well as the olfactory tubercle. The same groups of animals were also scored for motor activity and body posture after the injection of 5-HT, and only animals injected into the nucleus accumbens showed a statistically significant decrease in motor activity and an increase in the display of a flat body posture. 8-OH-DPAT (0-5 micrograms side-1), injected into the nucleus accumbens, produced a facilitation of the male rat sexual behavior, as evidenced by a decrease in number of mounts and intromissions to ejaculation, as well as in the postejaculatory interval. 8-OH-DPAT injections into the nucleus accumbens produced a decrease in motor activity and an increase in the per cent animals with a flat body posture. Injections into the olfactory tubercle had no effects on the sexual behavior or on the motor activity, whereas the per cent flat body posture was increased. Local application of 8-OH-DPAT (0-5 micrograms) into the median raphe nucleus, facilitated male rat sexual behavior, as evidenced by a decrease in number of intromissions preceding ejaculation and in time to ejaculation. The same doses of 8-OH-DPAT injected into the dorsal raphe had no effects on the sexual behavior. In an additional experiment, 3 groups of animals were injected with 5-HT (40 micrograms) or 8-OH-DPAT (5 micrograms) into the nucleus accumbens, the dorsal and the median raphe nuclei and thereafter observed for treadmill performance. No statistically significant effects were found after injections in any of these brain areas. The present results strongly suggest an inhibitory role of ventral forebrain 5-HT in the mediation of male rat sexual behavior. The facilitation produced by 8-OH-DPAT is possibly due to a blockade of 5-HT2 receptors. Facilitation by 8-OH-DPAT of the male rat copulatory performance after median raphe injections is probably due to stimulation of 5-HT1A autoreceptors in this brainstem region. In contrast to their opposite effects on sexual behavior, both compounds produced a decrease in motor activity and an increased display of flat body posture after accumbens injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphine and dynorphin(1-13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01-6 nmol) and dynorphin(1-13) (0.01-3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10-100 pmol) and dynorphin (10-100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1-10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.     

Pubertal development of penile reflexes and copulation in male rats

(1) Three groups of male rats were tested from 25 to 55 days of age for copulatory behavior, penile reflexes, or plasma testosterone (T). (2) Penile reflexes and copulatory behavior developed prior to the time of maximum T, but not before T had reached appreciable levels. (3) Penile reflex potential developed concurrently with copulation: the ages at which mounts, intromissions, and ejaculations first appeared were matched by the ages of appearance of penile erections, flips and cups respectively. (4) Of the behavioral measures, only penile cups and the ejaculatory pattern did not appear before preputial separation. (5) To the extent that laboratory rats are unique in having parallel development of copulatory behavior and penile reflexes, their value as a mammalian model of behavioral puberty is restricted.     

Terminal nerve damage impairs the mating behavior of the male hamster

We examined the effects of bilateral terminal nerve (TN) transections (TXx) on the sexual behavior to reach ejaculation. Damage to produced a decreased in mating frequency and/or an increase in the number of intromissions required to reach ejaculation. Damage to the olfactory bulbs or rostral forebrain did not account for these effects. No amelioration of the behavioral impairments occurred over the mating sessions. Basal testosterone levels in the blood of male hamsters were not altered by TN damage. Hamsters with TNx retained their ability to detect odors, but demonstrated reduced attraction to vaginal odors as compared with unoperated animals. The reduced attraction to vaginal odors was most pronounced in sporadically mating TNx animals. These data suggest that the TN may facilitate odor-induced sexual excitation in the male hamster.     

Risperidone-associated ejaculatory and urinary dysfunction in male adolescents

We report two male adolescents who developed partial or complete retrograde ejaculation during risperidone treatment. Additionally, one patient complained of bladder outflow obstruction, and the other reported a reduced ejaculatory volume and decreased viscosity of semen. On rechallenge with risperidone, patient A showed a prompt recurrence of the ejaculatory dysfunction. The side effects were highly disturbing and led to reduced treatment compliance in both patients. The impact of risperidone, a strong alpha(1)-receptor antagonist, on the adrenergic system might induce retrograde ejaculation by altering the sympathetic tonus, allowing semen to pass retrogradely into the bladder during ejaculation. The reduced ejaculatory volume may be caused by risperidone-induced hyperprolactinemia. Clinicians should regularly inquire about sexual dysfunction and symptoms suggestive of hyperprolactinemia before starting risperidone treatment and regularly thereafter.     

Penile reflexes and copulatory behavior in male rats following lesions in the bed nucleus of the stria terminalis

VALCOURT, R. J. AND B. D. SACHS. Penile reflexes and copulatory behavior in male rats following lesions in the bednucleus of the stria terminalis. BRAIN RES. BULL. 4(1) 131–133, 1979.—Male rats with large lesions in the bed nucleus of the stria terminalis (BNST) had more intromissions preceding ejaculation (if they ejaculated at all), longer intervals between intromissions, and longer postejaculatory refractory periods than control animals. In tests for penile reflexes, BNST males were similar to control males in every respect. The copulatory deficits in BNST males are probably not mediated by a change in penile reflex potential.     

Differential effects of the antiandrogen flutamide on aspects of sexual behavior in castrated, androgen-treated male rats

(1) This study focused on the question of whether the behavioral effects of the non-steroidal antiandrogen flutamide result from actions on CNS or peripheral mechanisms governing sexual behavior in male rats. (2) Restoration of sexual behavior in long-term male castrates was evaluated in response to administration of testosterone propionate (TP) with or without flutamide. (3) Two types of behavioral tests were employed—one was a standard test of the complete copulatory behavior pattern while the other involved anesthetization of the male's penis which served to reduce the role of peripheral factors in the male's behavior and eliminate intromission and ejaculatory behavior. (4) In the behavioral tests with genital anesthetization, flutamide facilitated mounting behavior. (5) Since mounting behavior in these tests presumably represents CNS function, facilitation of the behavior indicates that flutamide acts as an androgen, and not as an antindrogen, on CNS mechanisms. (6) In the behavioral complete copulatory behavior pattern, flutamide inhibited ejaculation and, to a lesser extent, intromission behavior. (7) Flutamide also completely inhibited the stimulatory effect of TP on peripheral structures. (8) It was concluded that the inhibitory effect of flutamide on ejaculation behavior resulted from deficiencies in peripheral, especially penile, structures although an alternative possibility—that flutamide differentially affects two CNS mechanisms governing mounting and ejaculation—cannot be excluded.     

Perinatal administration of nicotine alters subsequent sexual behavior and testosterone levels of male rats

The effect of pre- and/or postnatal administration of nicotine (0.25 mg/kg) on sexual behavior and testosterone levels in adult male rats was examined. Prenatal nicotine decreases male sexual behavior as measured by the number of males that mounted, intromitted or ejaculated. The males that did mount and/or ejaculate exhibited an increase in mount latency and number of mounts and a decrease in efficiency. This decrease was correlated with a decrease in plasma testosterone levels. Postnatal nicotine treatment improved the sexual performance of sexually naive males as measured by an increase in the number of males that completed 2 ejaculatory series and by a decrease in mount latency. This effect is transient, subsequent testing of the nicotine males eliminated this difference in sexual performance. Pre- and postnatal nicotine treatment did not affect the overall sexual performance of the male rats, although the number of mounts and intromissions during a second series decreased. Eye opening of male and female pups was accelerated with pre/postnatal nicotine administration. Birth weight, testis and levator ani weights, sex ration and number of pups per litter were not affected. We suggest that nicotine may act as a neuromodulator during sexual differentiation of the brain, demasculinizing the male progeny in rats. This effect is correlated with decreased testosterone levels during adulthood.     

Partial antagonism of 8-OH-DPAT'S effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist

The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT_1A receptor, it also acts at other receptor sites including the dopamine D₂ receptor. The current experiments investigated whether 8-OH-DPAT injected into the MPOA facilitates male sexual behavior through stimulation of the 5-HT_1A receptor or the dopamine D₂ receptor. Experiment 1 co-administered 8-OH-DPAT (6 μg) with either the 5-HT_1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (MPPI) (10 μg) or the D₂ antagonist raclopride (10 μg). Raclopride blocked 8-OH-DPAT's facilitative effects on ejaculation frequency and latency, while the 5-HT_1A antagonist was ineffective. In Experiment 2, 8-OH-DPAT (500 μM), retrodialyzed into the MPOA through a microdialysis probe, enhanced male copulatory behavior similarly to the microinjection, increasing ejaculation frequency and decreasing ejaculation latency, postejaculatory interval and mount frequency. Retrodialyzing 8-OH-DPAT through a microdialysis probe in the MPOA had been previously shown to increase extracellular levels of dopamine and serotonin. The data from the present studies suggest that the effects of 8-OH-DPAT in the MPOA on male rat copulatory behavior may be mediated, at least in part, either directly through 8-OH-DPAT's activity at D₂ receptors or indirectly through 8-OH-DPAT's ability to increase extracellular dopamine.